Significance Continuing our studies on intramembranous absorption defined as the direct fetal absorption from the amniotic cavity via fetal membranes and fine vessels on top of the placenta. We are currently investigating whether compounds administered into the amniotic cavity could become a method for direct fetal therapy. We've chosen to look at lung maturation associated with premature delivery. Clinical efforts to enhance lung maturation include maternal administration of betamethasone (BE) and thyroid releasing hormone (TRF). Objectives In the rhesus monkey, we have compare maternal injection (BE&TRH) to intraamniotic (IA) injections (BE, thyroid hormone (T4) to determine which rigime is superior for improving indices of fetal lung maturation. If IA therapy proves superb, future human fetal therapy may be as simple as administering a cocktail of agents at the time of diagnostic amniocentesis for a mother with preterm labor. Results This last year we performed studies on 4 animals, comparing the IA route of administration of BE and T4 (n = 2), with a maternal route of administration of BE and TRF (n = 2), and with a non-intervention control (n=2). Amniocentesis was performed on gestational day 125 for collection of amniotic fluid for determination of SP-A. After amniocentesis, 2 animals received BE (2 mg) IM to the mother and repeated in 24 hours. In addition, TRF (400 ug) was given IV to the mother every 6 hours for 24 hours. In another animals, BE (1 mg) and T4 (60 ug) were injected into the amniotic cavity at the time of amniocentesis. In the last animal saline was injected into the amniotic cavity. Seventy-two hours later, the fetuses were harvested by hysterotomy and tissue and amniotic fluid was collected. Future Directions The amniotic fluid SP-A was found to increase by 18.8 1 0.5% (P <0.01) at 72 hour in the IA group while decreasing by 5.9 1 5.0% in the maternally treated animals. Immunohistochemical staining of fetal lung for SP-A was increased in the IA lung tissue as compared to the maternal therapy group and the control group. It is our intention to continue along with this same study to increase the numbers in each experimental group until statistical significance is reached (i.e. 6/group). KEY WORDS amniotic injection, prematurity, betamethasone, thyroid releasing hormone FUNDING NIH Grant HD10342